Anti-bcma chimeric antigen receptors

Abstract

Provided herein are chimeric antigen receptors (CARs), such as those specific for BCMA, that have improved properties, including increased CAR T cell binding to BCMA and improved CAR T cell killing of BCMA-expressing cancer cells. Use of the CARs in immune cells (e.g., T cells), compositions (e.g., CARs and nucleic acid constructs encoding the same), and methods are also contemplated.

1 - 133 . (canceled) 
     
     
         134 . A nucleic acid encoding a protein comprising an antigen-binding portion, wherein the antigen binding portion is an anti-B-Cell Maturation Antigen (BCMA) binding domain comprising:
 a heavy chain complementarity determining region 1 (CDRH1) comprising any one of SEQ ID NOs: 1-3;   a heavy chain complementarity determining region 2 (CDRH2) comprising any one of SEQ ID NOs: 4-6;   a heavy chain complementarity determining region 3 (CDRH3) comprising any one of SEQ ID NOs: 7-9;   a light chain complementarity determining region 1 (CDRL1) comprising any one of SEQ ID NOs: 10-11;   a light chain complementarity determining region 2 (CDRL2) comprising any one of SEQ ID NOs: 12-15; and   a light chain complementarity determining region 3 (CDRL3) comprising any one of SEQ ID NOs: 16-18;   provided that the anti-BCMA binding domain does not comprise all six of the following:   a CDRH1 comprising SEQ ID NO: 1;   a CDRH2 comprising SEQ ID NO: 4;   a CDRH3 comprising SEQ ID NO: 7;   a CDRL1 comprising SEQ ID NO: 10;   a CDRL2 comprising SEQ ID NO: 12; and   a CDRL3 comprising SEQ ID NO: 16.   
     
     
         135 . The nucleic acid of  claim 134 , wherein the nucleic acid is mRNA. 
     
     
         136 . The mRNA of  claim 135 , wherein the CDRH1 comprises SEQ ID NO: 1. 
     
     
         137 . The mRNA of  claim 135 , wherein the CDRH1 comprises SEQ ID NO: 2. 
     
     
         138 . The mRNA of  claim 135 , wherein the CDRH1 comprises SEQ ID NO: 3. 
     
     
         139 . The mRNA of  claim 135 , wherein the CDRH2 comprises SEQ ID NO: 4. 
     
     
         140 . The mRNA of  claim 135 , wherein the CDRH2 comprises SEQ ID NO: 5. 
     
     
         141 . The mRNA of  claim 135 , wherein the CDRH2 comprises SEQ ID NO: 6. 
     
     
         142 . The mRNA of  claim 135 , wherein the CDRH3 comprises SEQ ID NO: 7. 
     
     
         143 . The mRNA of  claim 135 , wherein the CDRH3 comprises SEQ ID NO: 8. 
     
     
         144 . The mRNA of  claim 135 , wherein the CDRH3 comprises SEQ ID NO: 9. 
     
     
         145 . The mRNA of  claim 135 , wherein the CDRL1 comprises SEQ ID NO: 10. 
     
     
         146 . The mRNA of  claim 135 , wherein the CDRL1 comprises SEQ ID NO: 11. 
     
     
         147 . The mRNA of  claim 135 , wherein the CDRL2 comprises SEQ ID NO: 12. 
     
     
         148 . The mRNA of  claim 135 , wherein the CDRL2 comprises SEQ ID NO: 13. 
     
     
         149 . The mRNA of  claim 135 , wherein the CDRL2 comprises SEQ ID NO: 14. 
     
     
         150 . The mRNA of  claim 135 , wherein the CDRL2 comprises SEQ ID NO: 15. 
     
     
         151 . The mRNA of  claim 135 , wherein the CDRL2 comprises SEQ ID NO: 16. 
     
     
         152 . The mRNA of  claim 135 , wherein the CDRL2 comprises SEQ ID NO: 17. 
     
     
         153 . The mRNA of  claim 135 , wherein the CDRL2 comprises SEQ ID NO: 18. 
     
     
         154 . The mRNA of  claim 135 , wherein the CDRH1 comprises SEQ ID NO: 1; the CDRH2 comprises SEQ ID NO: 4; the CDRH3 comprises SEQ ID NO: 8; the CDRL1 comprises SEQ ID NO: 10; the CDRL2 comprises SEQ ID NO: 15; and the CDRL3 comprises SEQ ID NO: 17. 
     
     
         155 . The mRNA of  claim 135 , wherein the CDRH1 comprises SEQ ID NO: 2; the CDRH2 comprises SEQ ID NO: 6; the CDRH3 comprises SEQ ID NO: 9; the CDRL1 comprises SEQ ID NO: 11; the CDRL2 comprises SEQ ID NO: 14; and the CDRL3 comprises SEQ ID NO: 17. 
     
     
         156 . The mRNA of  claim 135 , wherein the CDRH1 comprises SEQ ID NO: 2; the CDRH2 comprises SEQ ID NO: 6; the CDRH3 comprises SEQ ID NO: 9; the CDRL1 comprises SEQ ID NO: 11; the CDRL2 comprises SEQ ID NO: 15; and the CDRL3 comprises SEQ ID NO: 17.